The parent compound used in the preparation of the compounds according to the present invention, 3R,4R-ethyl-[(1-methyl-1H-imidazol-5-yl) methyl]-2-pyrrolidinone, is known in the art, and, together with other 1-alkyl substituted derivatives of the same basic structure, is disclosed in the U.S. Pat. No. 3,470,197. There, it and certain derivatives are described as useful as antiglaucoma agents. Koda, et al., J. Pharm. Sciences, 62, 2021 (1973) describes certain of the compounds of U.S. Pat. No. 3,470,197 as possessing cholinergic activity.
Structurally, the parent compound is related to the corresponding lactone, from which it can be prepared. The lactone is a known antiglaucoma agent: 3S,4R-3-ethyl-4-[(1-methyl-1H-imidazol-5-yl) methyl]-3,4-dihydro-2(3H)-furanone (pilocarpine). Both compounds lower intraocular pressure via contraction of the ciliary muscle, and also cause simultaneous contraction of the iris muscle leading to decrease in pupil diameter (miosis) in the patient's eye following topical administration. Pilocarpine is an optically active (3S,4R) compound that is stereoisomeric with isopilocarpine, the optically active trans-isomer (3R,4R). Although pilocarpine is one of the commonly used outflow enhancing drugs used for glaucoma therapy, its use is limited because of its short duration. Our major objective has been to develop pilocarpine analogues with increased duration of action and improved corneal penetration over pilocarpine.